Current Treatment Strategies in Breast Cancer Brain Metastases

Abstract

Brain metastases (BM) are a deleterious complication of breast cancer (BC) as BM increase disease-related morbidity and mortality and are commonly regarded as the greatest conceivable threat for patients at risk. A growing incidence of BC BM was observed over the last two decades, mainly linked to advances in extracranial disease control by improved systemic therapy and broader availability of MRT for screening purposes. Local treatment strategies such as neurosurgical resection, radiosurgery, stereotactic radiotherapy and whole-brain radiotherapy remain the standard of care. In contrast, systemic therapy played only a minor role to date as the blood–brain barrier (BBB) was traditionally believed to prevent antitumour drugs from reaching clinically relevant concentrations within BM. Recently, this belief was challenged as significant clinical activity of lapatinib, a HER2-targeting tyrosine kinase inhibitor, in combination with capecitabine in progressive and previously untreated BM was observed. Other data even suggest clinical activity of larger molecules such as the antibody-drug conjugate trastuzumab-DM1 in BM as the BBB is impaired at the metastatic site. This observation is well in line with historic publications reporting on the activity of conventional chemotherapy in BM and opens the path for systemic therapy of BM in other BC subtypes beyond HER2.